The objectives of this research are the synthesis, the unequivocal characterization, and the initial biological screening of a complete series of 5-oxo and 7oxopyrido(2,3-d) pyrimidine ribonucleosides as potential antitumor agents which are structurally related to the pyrrolo(2,3-d)pyrimidine nucleoside antibiotics Tubercidin, toyocomycin, and sangivamycin. The synthesis will be by a combination of procedures including preparation or requisite pyrido(2,3-d)pyrimidine bases, sugar-base coupling methods, and interconversions at the nucleoside level. New methods for the synthesis of the 2-amino and 2-fluoro analogs of target nucleosides will be investigated. Proof of structure will be based on unequivocal synthetic methods and intrumental analysis. Proof of anomeric configuration will be by conversion to the 3,5' cyclonucleoside. The pyridopyrimidine nucleosides including the 2-substituted analogs will be evaluated biologically using enzymatic assays and in vivo evaluation for antitumor activity. Stability to the catabolic enzyme, adenosine deaminase, will be determined, based on the known inactivity of the pyrrolo(2,3-d)pyrimidine nucleosides to this enzyme. The requirement that these nucleosides will require biological activation to the nucleotide level similar to tubercidin will be determined using the enzyme adenosine kinase. The results of the biological studies will be correlated for structure-activity relationships within the series of nucleosides, which will allow evaluation of these compounds to serve as unique alternatives to the many compounds of biological importance containing adenosine. These compounds may serve as useful probes in the determination of the mechanism of cytotoxicity of the pyrrolo(2,3-d)pyrimidine nucleosides.